Intro

In this episode, Keith Flaherty, director of clinical research and targeted cancer therapy at Massachusetts General Hospital, shares his vast wealth of knowledge in cancer starting with the history of treatment from chemotherapy to radiation to surgical therapy and where those methodologies seemed to have leveled off. He also walks us through the timeline of advancements (and lack there of) from when the War on Cancer was declared in the 1970s, through the sequencing of the entire human genome, and all the way to today. Keith dives into the topic of immunotherapy, probably the most exciting recent development in cancer therapy, and also provides us a rundown of his notion of a different approach to cancer that attacks all the essential pillars of cancer growth and survival. Finally, we talk a little bit about liquid biopsies, we discuss the roles of CRISPR and other potentially over-hyped therapies with respect to cancer. We also touch on stem cell therapy a bit, as well as some other common cancer-related questions such as the role of vitamin D and sun exposure in melanoma, and much more.

We discuss:

• Growing up around medicine, and finding a career that you love [7:30];
• Medicine as a career, limitations of the med school teaching approach, and the dynamic and accelerating field of medicine and technology [16:30];
• Explaining chemotherapy, radiation, and how a cancer develops [23:45];
• Surgical oncology, cure rate of solid tumors, and survival rate after tumor removal  [33:15];
• 25 years after the War on Cancer is declared, gene sequencing, and why Keith’s was fascinated by the HIV case study [37:15];
• Cancer immunotherapy: History, how it works, and why some cancers respond and others don’t [46:00];
• MHC complexes, and cancer cloaking mechanisms [56:00];
• Comparative biology of cancer: Why some cancer can evade immune detection better than others [1:03:00];
• What we learned from the Cancer Genome Atlas Project [1:07:00];
• Defining targeted therapy, HER2 breast cancer, chronic leukemia, and the translocation of chromosomes [1:12:00];
• Tumor protein P53, the most famous tumor suppressor gene and its ubiquity in cancer [1:17:45];
• Activated oncogenes, the RAS pathway, PI3 kinase, RAF gene, and Keith’s “aha moment” [1:24:15];
• Advice for starting your career as a scientist/clinician [1:37:00];
• Fusion-driven cancers, targeted therapy, and the Bcr-Abl/chronic myelogenous leukemia case study [1:39:45];
• Targeted therapy for fusion-driven solid tumors, adjuvant systemic therapy, and the HER2 breast cancer example [1:53:00];
• Advancing melanoma treatment, survival, and cure rates with BRAF-MEK combo therapy [1:59:15];
• The fundamental pillars of cancer growth and survival, and the toolkit we need to attack cancer from all angles [2:02:40];
• Peter’s clinical framework for thinking about cancer and how Keith might improve it, and how the biotech environment is hampering our ability to put together novel cancer treatments [2:05:00];
• How useful is CRISPR in terms of tumor suppressing? [2:16:15];
• Liquid biopsies as a therapeutic monitoring tool [2:18:00];
• Stem cell therapy: The efficacy and potential risks [2:25:15];
• Aging and cancer: Is cancer inevitable? [2:28:45];
• Vitamin D supplements, sun exposure, melanoma, and exercise [2:32:30];
• How and why Keith has straddled the line between science/research and industry/drug companies, and the importance of getting more voices of practitioners at the table [2:42:00]; and
• More.

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